Magnetic resonance imaging as a noninvasive adjunct to conventional assessment of functional differences between kidneys in vivo and during ex vivo normothermic machine perfusion.

Normothermic machine perfusion (NMP) is increasingly considered for pretransplant kidney quality assessment. However, fundamental questions about differences between in vivo and ex vivo renal function, as well as the impact of ischemic injury on ex vivo physiology, remain unanswered. This study utilized magnetic resonance imaging (MRI), alongside conventional parameters to explore differences between in vivo and ex vivo renal function and the impact of warm ischemia on a kidney's behavior ex vivo. Renal MRI scans and samples were obtained from living pigs (n = 30) in vivo. Next, kidney pairs were procured and exposed to minimal, or 75 minutes of warm ischemia, followed by 6 hours of hypothermic machine perfusion. Both kidneys simultaneously underwent 6-hour ex vivo perfusion in MRI-compatible NMP circuits to obtain multiparametric MRI data. Ischemically injured ex vivo kidneys showed a significantly altered regional blood flow distribution compared to in vivo and minimally damaged organs. Both ex vivo groups showed diffusion restriction relative to in vivo. Our findings underscore the differences between in vivo and ex vivo MRI-based renal characteristics. Therefore, when assessing organ viability during NMP, it should be considered to incorporate parameters beyond the conventional functional markers that are common in vivo.

Quantification of P-glycoprotein function at the human blood-brain barrier using [18F]MC225 and PET.

INTRODUCTION: P-glycoprotein (P-gp) is one of the most studied efflux transporters at the blood-brain barrier. It plays an important role in brain homeostasis by protecting the brain from a variety of endogenous and exogeneous substances. Changes in P-gp function are associated both with the onset of neuropsychiatric diseases, including Alzheimer's disease and Parkinson's disease, and with drug-resistance, for example in treatment-resistant depression. The most widely used approach to measure P-gp function in vivo is (R)-[11C]verapamil PET. (R)-[11C]verapamil is, however, an avid P-gp substrate, which complicates the use of this tracer to measure an increase in P-gp function as its baseline uptake is already very low. [18F]MC225 was developed to measure both increases and decreases in P-gp function. AIM: The aim of this study was (1) to identify the pharmacokinetic model that best describes [18F]MC225 kinetics in the human brain and (2) to determine test-retest variability. METHODS: Five (2 male, 3 female) of fourteen healthy subjects (8 male, 6 female, age 67 ± 5 years) were scanned twice (injected dose 201 ± 47 MBq) with a minimum interval of 2 weeks between scans. Each scanning session consisted of a 60-min dynamic [18F]MC225 scan with continuous arterial sampling. Whole brain grey matter data were fitted to a single tissue compartment model, and to reversible and irreversible two tissue-compartment models to obtain various outcome parameters (in particular the volume of distribution (VT), Ki, and the rate constants K1 and k2). In addition, a reversible two-tissue compartment model with fixed k3/k4 was included. The preferred model was selected based on the weighted Akaike Information Criterion (AIC) score. Test-retest variability (TRTV) was determined to assess reproducibility. RESULTS: Sixty minutes post-injection, the parent fraction was 63.8 ± 4.0%. The reversible two tissue compartment model corrected for plasma metabolites with an estimated blood volume (VB) showed the highest AIC weight score of 34.3 ± 17.6%. The TRVT of the VT for [18F]MC225 PET scans was 28.3 ± 20.4% for the whole brain grey matter region using this preferred model. CONCLUSION: [18F]MC225 VT, derived using a reversible two-tissue compartment model, is the preferred parameter to describe P-gp function in the human BBB. This outcome parameter has an average test-retest variability of 28%. TRIAL REGISTRATION: EudraCT 2020-001564-28 . Registered 25 May 2020.

Prediction of pseudoprogression in post-treatment glioblastoma using dynamic susceptibility contrast-derived oxygenation and microvascular transit time heterogeneity measures.

OBJECTIVES: To evaluate the added value of MR dynamic susceptibility contrast (DSC)-perfusion-weighted imaging (PWI)-derived tumour microvascular and oxygenation information with cerebral blood volume (CBV) to distinguish pseudoprogression from true progression (TP) in post-treatment glioblastoma. METHODS: This retrospective single-institution study included patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma and a newly developed or enlarging measurable contrast-enhancing mass within 12 weeks after concurrent chemoradiotherapy. CBV, capillary transit time heterogeneity (CTH), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) were obtained from DSC-PWI. Predictors were selected using univariable logistic regression, and performance was measured with adjusted diagnostic odds with tumour volume and area under the curve (AUC) of receiver operating characteristics analysis. RESULTS: A total of 103 patients were included (mean age, 59.6 years; 59 women), with 67 cases of TP and 36 cases of pseudoprogression. Pseudoprogression exhibited higher CTH (4.0 vs. 3.4, p = .019) and higher OEF (12.7 vs. 10.7, p = .014) than TP, but a similar CBV (1.48 vs. 1.53, p = .13) and CMRO2 (7.7 vs. 7.3s, p = .598). Independent of tumour volume, both high CTH (adjusted odds ratio [OR] 1.52; 95% confidence interval [CI]: 1.11-2.09, p = .009) and high OEF (adjusted OR 1.17; 95% CI:1.03-1.33, p = .016) were predictors of pseudoprogression. The combination of CTH, OEF, and CBV yielded higher diagnostic performance (AUC 0.71) than CBV alone (AUC 0.65). CONCLUSION: High intratumoural capillary transit heterogeneity and high oxygen extraction fraction derived from DSC-PWI have enhanced the diagnostic value of CBV in pseudoprogression of post-treatment IDH-wild type glioblastoma. CLINICAL RELEVANCE STATEMENT: In the early post-treatment stage of glioblastoma, pseudoprogression exhibited both high oxygen extraction fraction and high capillary transit heterogeneity and these dynamic susceptibility contrast-perfusion weighted imaging derived parameters have added value in cerebral blood volume-based noninvasive differentiation of pseudoprogression from true progression. KEY POINTS: • Capillary transit time heterogeneity and oxygen extraction fraction can be measured noninvasively through processing of dynamic susceptibility contrast imaging. • Pseudoprogression exhibited higher capillary transit time heterogeneity and higher oxygen extraction fraction than true progression. • A combination of cerebral blood volume, capillary transit time heterogeneity, and oxygen extraction fraction yielded the highest diagnostic performance (area under the curve 0.71).

Magnetic resonance imaging during warm ex vivo kidney perfusion.

BACKGROUND: The shortage of donor organs for transplantation remains a worldwide problem. The utilization of suboptimal deceased donors enlarges the pool of potential organs, yet consequently, clinicians face the difficult decision of whether these sub-optimal organs are of sufficient quality for transplantation. Novel technologies could play a pivotal role in making pre-transplant organ assessment more objective and reliable. METHODS: Ex vivo normothermic machine perfusion (NMP) at temperatures around 35-37°C allows organ quality assessment in a near-physiological environment. Advanced magnetic resonance imaging (MRI) techniques convey unique information about an organ's structural and functional integrity. The concept of applying magnetic resonance imaging during renal normothermic machine perfusion is novel in both renal and radiological research and we have developed the first MRI-compatible NMP setup for human-sized kidneys. RESULTS: We were able to obtain a detailed and real-time view of ongoing processes inside renal grafts during ex vivo perfusion. This new technique can visualize structural abnormalities, quantify regional flow distribution, renal metabolism, and local oxygen availability, and track the distribution of ex vivo administered cellular therapy. CONCLUSION: This platform allows for advanced pre-transplant organ assessment, provides a new realistic tool for studies into renal physiology and metabolism, and may facilitate therapeutic tracing of pharmacological and cellular interventions to an isolated kidney.

EARL compliance and imaging optimisation on the Biograph Vision Quadra PET/CT using phantom and clinical data.

PURPOSE: Current European Association of Nuclear Medicine (EANM) Research Ltd. (EARL) guidelines for the standardisation of PET imaging developed for conventional systems have not yet been adjusted for long axial field-of-view (LAFOV) systems. In order to use the LAFOV Siemens Biograph Vision Quadra PET/CT (Siemens Healthineers, Knoxville, TN, USA) in multicentre research and harmonised clinical use, compliance to EARL specifications for 18F-FDG tumour imaging was explored in the current study. Additional tests at various locations throughout the LAFOV and the use of shorter scan durations were included. Furthermore, clinical data were collected to further explore and validate the effects of reducing scan duration on semi-quantitative PET image biomarker accuracy and precision when using EARL-compliant reconstruction settings. METHODS: EARL compliance phantom measurements were performed using the NEMA image quality phantom both in the centre and at various locations throughout the LAFOV. PET data (maximum ring difference (MRD) = 85) were reconstructed using various reconstruction parameters and reprocessed to obtain images at shorter scan durations. Maximum, mean and peak activity concentration recovery coefficients (RC) were obtained for each sphere and compared to EARL standards specifications. Additionally, PET data (MRD = 85) of 10 oncological patients were acquired and reconstructed using various reconstruction settings and reprocessed from 10 min listmode acquisition into shorter scan durations. Per dataset, SUVs were derived from tumour lesions and healthy tissues. ANOVA repeated measures were performed to explore differences in lesion SUVmax and SUVpeak. Wilcoxon signed-rank tests were performed to evaluate differences in background SUVpeak and SUVmean between scan durations. The coefficient of variation (COV) was calculated to characterise noise. RESULTS: Phantom measurements showed EARL compliance for all positions throughout the LAFOV for all scan durations. Regarding patient data, EARL-compliant images showed no clinically meaningful significant differences in lesion SUVmax and SUVpeak or background SUVmean and SUVpeak between scan durations. Here, COV only varied slightly. CONCLUSION: Images obtained using the Vision Quadra PET/CT comply with EARL specifications. Scan duration and/or activity administration can be reduced up to a factor tenfold without the interference of increased noise.

Myelin quantification with MRI: A systematic review of accuracy and reproducibility.

OBJECTIVES: Currently, multiple sclerosis is treated with anti-inflammatory therapies, but these treatments lack efficacy in progressive disease. New treatment strategies aim to repair myelin damage and efficacy evaluation of such new therapies would benefit from validated myelin imaging techniques. Several MRI methods for quantification of myelin density are available now. This systematic review aims to analyse the performance of these MRI methods. METHODS: Studies comparing myelin quantification by MRI with histology, the current gold standard, or assessing reproducibility were retrieved from PubMed/MEDLINE and Embase (until December 2019). Included studies assessed both myelin histology and MRI quantitatively. Correlation or variance measurements were extracted from the studies. Non-parametric tests were used to analyse differences in study methodologies. RESULTS: The search yielded 1348 unique articles. Twenty-two animal studies and 13 human studies correlated myelin MRI with histology. Eighteen clinical studies analysed the reproducibility. Overall bias risk was low or unclear. All MRI methods performed comparably, with a mean correlation between MRI and histology of R2=0.54 (SD=0.30) for animal studies, and R2=0.54 (SD=0.18) for human studies. Reproducibility for the MRI methods was good (ICC=0.75-0.93, R2=0.90-0.98, COV=1.3-27%), except for MTR (ICC=0.05-0.51). CONCLUSIONS: Overall, MRI-based myelin imaging methods show a fairly good correlation with histology and a good reproducibility. However, the amount of validation data is too limited and the variability in performance between studies is too large to select the optimal MRI method for myelin quantification yet.

Long axial field of view PET scanners: a road map to implementation and new possibilities.

In this contribution, several opportunities and challenges for long axial field of view (LAFOV) PET are described. It is an anthology in which the main issues have been highlighted. A consolidated overview of the camera system implementation, business and financial plan, opportunities and challenges is provided. What the nuclear medicine and molecular imaging community can expect from these new PET/CT scanners is the delivery of more comprehensive information to the clinicians for advancing diagnosis, therapy evaluation and clinical research.

An international expert opinion statement on the utility of PET/MR for imaging of skeletal metastases.

BACKGROUND: MR is an important imaging modality for evaluating musculoskeletal malignancies owing to its high soft tissue contrast and its ability to acquire multiparametric information. PET provides quantitative molecular and physiologic information and is a critical tool in the diagnosis and staging of several malignancies. PET/MR, which can take advantage of its constituent modalities, is uniquely suited for evaluating skeletal metastases. We reviewed the current evidence of PET/MR in assessing for skeletal metastases and provided recommendations for its use. METHODS: We searched for the peer reviewed literature related to the usage of PET/MR in the settings of osseous metastases. In addition, expert opinions, practices, and protocols of major research institutions performing research on PET/MR of skeletal metastases were considered. RESULTS: Peer-reviewed published literature was included. Nuclear medicine and radiology experts, including those from 13 major PET/MR centers, shared the gained expertise on PET/MR use for evaluating skeletal metastases and contributed to a consensus expert opinion statement. [18F]-FDG and non [18F]-FDG PET/MR may provide key advantages over PET/CT in the evaluation for osseous metastases in several primary malignancies. CONCLUSION: PET/MR should be considered for staging of malignancies where there is a high likelihood of osseous metastatic disease based on the characteristics of the primary malignancy, hight clinical suspicious and in case, where the presence of osseous metastases will have an impact on patient management. Appropriate choice of tumor-specific radiopharmaceuticals, as well as stringent adherence to PET and MR protocols, should be employed.

Magnetic resonance imaging assessment of renal flow distribution patterns during ex vivo normothermic machine perfusion in porcine and human kidneys.

Acceptance criteria of deceased donor organs have gradually been extended toward suboptimal quality, posing an urgent need for more objective pre-transplant organ assessment. Ex vivo normothermic machine perfusion (NMP) combined with magnetic resonance imaging (MRI) could assist clinicians in deciding whether a donor kidney is suitable for transplantation. Aim of this study was to characterize the regional distribution of perfusate flow during NMP, to better understand how ex vivo kidney assessment protocols should eventually be designed. Nine porcine and 4 human discarded kidneys underwent 3 h of NMP in an MRI-compatible perfusion setup. Arterial spin labeling scans were performed every 15 min, resulting in perfusion-weighted images that visualize intrarenal flow distribution. At the start of NMP, all kidneys were mainly centrally perfused and it took time for the outer cortex to reach its physiological dominant perfusion state. Calculated corticomedullary ratios based on the perfusion maps reached a physiological range comparable to in vivo observations, but only after 1 to 2 h after the start of NMP. Before that, the functionally important renal cortex appeared severely underperfused. Our findings suggest that early functional NMP quality assessment markers may not reflect actual physiology and should therefore be interpreted with caution.

Blood Oxygen Level-Dependent MRI of the Myocardium with Multiecho Gradient-Echo Spin-Echo Imaging.

Background Myocardial oxygenation imaging could help determine the presence of microvascular dysfunction associated with increased cardiovascular risk. However, it is challenging to depict the potentially small oxygenation alterations with current noninvasive cardiac MRI blood oxygen level-dependent (BOLD) techniques. Purpose To demonstrate the cardiac application of a gradient-echo spin-echo (GESE) echo-planar imaging sequence for dynamic and quantitative heartbeat-to-heartbeat BOLD MRI and evaluate the sequence in populations both healthy and with hypertension in combination with a breath hold-induced CO2 intervention. Materials and Methods GESE echo-planar imaging sequence was performed in 18 healthy participants and in eight prospectively recruited participants with hypertension on a 3.0-T MRI system. T2 and T2* maps were calculated per heartbeat with a four-parameter fitting technique. Septal regions of interests were used to determine T2 and T2* values per heartbeat and examined over the course of a breath hold to determine BOLD changes. T2 and T2* changes of healthy participants and participants with hypertension were compared by using a nonparametric Mann-Whitney test. Results GESE echo-planar imaging approach gave spatially stable T2 and T2* maps per heartbeat for healthy participants and participants with hypertension, with mean T2 values of 43 msec ± 5 (standard deviation) and 46 msec ± 9, respectively, and mean T2* values of 28 msec ± 5 and 22 msec ± 5, respectively. The healthy participants exhibited increasing T2 and T2* values over the course of a breath hold with a mean positive slope of 0.2 msec per heartbeat ± 0.1 for T2 and 0.2 msec per heartbeat ± 0.1 for T2*, whereas for participants with hypertension these dynamic T2 and T2* values had a mean negative slope of -0.2 msec per heartbeat ± 0.2 for T2 and -0.1 msec per heartbeat ± 0.2 for T2*. The difference in these mean slopes between healthy participants and participants with hypertension was significant for both T2 (P < .001) and T2* (P < .001). Conclusion Gradient-echo spin-echo echo-planar imaging sequence provided quantitative T2 and T2* maps per heartbeat and enabled dynamic heartbeat-to-heartbeat blood oxygen level-dependent (BOLD)-response imaging by analyzing changes in T2 and T2* over the time of a breath-hold intervention. This approach could identify differences in the BOLD response between healthy participants and participants with hypertension. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Friedrich in this issue.

Software reproducibility of myocardial blood flow and flow reserve quantification in ischemic heart disease: A 13N-ammonia PET study.

BACKGROUND: We explored agreement in the quantification of myocardial perfusion by cross-comparison of implemented software packages (SPs) in three distinguishable patient profile populations. METHODS: We studied 91 scans of patients divided into 3 subgroups based on their semi-quantitative perfusion findings: patients with normal perfusion, with reversible perfusion defects, and with fixed perfusion defects. Rest myocardial blood flow (MBF), stress MBF, and myocardial flow reserve (MFR) were obtained with QPET, SyngoMBF, and Carimas. Agreement between SPs was considered adequate when a pairwise standardized difference was found to be < 0.20 and its corresponding intraclass correlation coefficient was ≥ 0.75. RESULTS: In patients with normal perfusion, two out of three comparisons of global stress MBF quantifications were outside the limits of agreement. In ischemic patients, all comparisons of global stress MBF and MFR were outside the limits of established agreement. In patients with fixed perfusion defects, all SP comparisons of perfusion quantifications were within the limit of agreement. Regionally, agreement of these perfusion estimates was mostly found for the left anterior descending artery vascular territory. CONCLUSION: Reversible defects demonstrated the worst agreement in global stress MBF and MFR and discrepancies showed to be regional dependent. Reproducibility between SPs should not be assumed.

MRI for diagnosis of post-renal transplant complications: current state-of-the-art and future perspectives.

Kidney transplantation has developed into a widespread procedure to treat end stage renal failure, with transplantation results improving over the years. Postoperative complications have decreased over the past decades, but are still an important cause of morbidity and mortality. Early accurate diagnosis and treatment is the key to prevent renal allograft impairment or even graft loss. Ideally, a diagnostic tool should be able to detect post-transplant renal dysfunction, differentiate between the different causes and monitor renal function during and after therapeutic interventions. Non-invasive imaging modalities for diagnostic purposes show promising results. Magnetic resonance imaging (MRI) techniques have a number of advantages, such as the lack of ionizing radiation and the possibility to obtain relevant tissue information without contrast, reducing the risk of contrast-induced nephrotoxicity. However, most techniques still lack the specificity to distinguish different types of parenchymal diseases. Despite some promising outcomes, MRI is still barely used in the post-transplantation diagnostic process. The aim of this review is to survey the current literature on the relevance and clinical applicability of diagnostic MRI modalities for the detection of various types of complications after kidney transplantation.

Native T1 reference values for nonischemic cardiomyopathies and populations with increased cardiovascular risk: A systematic review and meta-analysis.

BACKGROUND: Although cardiac MR and T1 mapping are increasingly used to diagnose diffuse fibrosis based cardiac diseases, studies reporting T1 values in healthy and diseased myocardium, particular in nonischemic cardiomyopathies (NICM) and populations with increased cardiovascular risk, seem contradictory. PURPOSE: To determine the range of native myocardial T1 value ranges in patients with NICM and populations with increased cardiovascular risk. STUDY TYPE: Systemic review and meta-analysis. POPULATION: Patients with NICM, including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), and patients with myocarditis (MC), iron overload, amyloidosis, Fabry disease, and populations with hypertension (HT), diabetes mellitus (DM), and obesity. FIELD STRENGTH/SEQUENCE: (Shortened) modified Look-Locker inversion-recovery MR sequence at 1.5 or 3T. ASSESSMENT: PubMed and Embase were searched following the PRISMA guidelines. STATISTICAL TESTS: The summary of standard mean difference (SMD) between the diseased and a healthy control populations was generated using a random-effects model in combination with meta-regression analysis. RESULTS: The SMD for HCM, DCM, and MC patients were significantly increased (1.41, 1.48, and 1.96, respectively, P < 0.01) compared with healthy controls. The SMD for HT patients with and without left-ventricle hypertrophy (LVH) together was significantly increased (0.19, P = 0.04), while for HT patients without LVH the SMD was zero (0.03, P = 0.52). The number of studies on amyloidosis, iron overload, Fabry disease, and HT patients with LVH did not meet the requirement to perform a meta-analysis. However, most studies reported a significantly increased T1 for amyloidosis and HT patients with LVH and a significant decreased T1 for iron overload and Fabry disease patients. DATA CONCLUSIONS: Native T1 mapping by using an (Sh)MOLLI sequence can potentially assess myocardial changes in HCM, DCM, MC, iron overload, amyloidosis, and Fabry disease compared to controls. In addition, it can help to diagnose left-ventricular remodeling in HT patients. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:891-912.

Enhanced fatty acid uptake in visceral adipose tissue is not reversed by weight loss in obese individuals with the metabolic syndrome.

AIMS/HYPOTHESIS: Obesity causes an imbalance in fat mass distribution between visceral and subcutaneous adipose tissue (AT) depots. We tested the hypothesis that this relates to increased NEFA uptake between these depots in obese compared with healthy participants. Second, we hypothesised that a diet very low in energy (very low calorie diet [VLCD]) decreases fat mass in obese participants and that this is associated with the decline in NEFA uptake. METHODS: NEFA uptake in AT depots was measured with [(18)F]-fluoro-6-thia-heptadecanoic acid ((18)F-FTHA) and positron emission tomography (PET) in 18 obese participants with the metabolic syndrome before and after a 6 week VLCD. Whole body fat oxidation was measured using indirect calorimetry and [U-(13)C]palmitate. Sixteen non-obese participants were controls. RESULTS: Obese participants had >100% higher (p < 0.0001) NEFA uptake in the visceral and subcutaneous abdominal AT depots than controls. VLCD decreased AT mass in all regions (12% to 21%), but NEFA uptake was decreased significantly (18%; p < 0.006) only in the femoral AT. Whole body carbohydrate oxidation decreased, while fat oxidation increased. CONCLUSIONS/INTERPRETATION: The data demonstrate that weight loss caused by VLCD does not affect abdominal fasting NEFA uptake rates. We found that visceral fat takes up more NEFAs than subcutaneous AT depots, even after weight loss.

Consensus paper: the role of the cerebellum in perceptual processes.

Various lines of evidence accumulated over the past 30 years indicate that the cerebellum, long recognized as essential for motor control, also has considerable influence on perceptual processes. In this paper, we bring together experts from psychology and neuroscience, with the aim of providing a succinct but comprehensive overview of key findings related to the involvement of the cerebellum in sensory perception. The contributions cover such topics as anatomical and functional connectivity, evolutionary and comparative perspectives, visual and auditory processing, biological motion perception, nociception, self-motion, timing, predictive processing, and perceptual sequencing. While no single explanation has yet emerged concerning the role of the cerebellum in perceptual processes, this consensus paper summarizes the impressive empirical evidence on this problem and highlights diversities as well as commonalities between existing hypotheses. In addition to work with healthy individuals and patients with cerebellar disorders, it is also apparent that several neurological conditions in which perceptual disturbances occur, including autism and schizophrenia, are associated with cerebellar pathology. A better understanding of the involvement of the cerebellum in perceptual processes will thus likely be important for identifying and treating perceptual deficits that may at present go unnoticed and untreated. This paper provides a useful framework for further debate and empirical investigations into the influence of the cerebellum on sensory perception.

First D1-like receptor PET imaging of the rat and primate kidney: implications for human disease monitoring.

The intrarenal dopamine system is important for signaling and natriuresis, and significant dysfunction is associated with hypertension and kidney disease in ex vivo studies. Dopamine receptors also modulate and are modulated by the renin-angiotensin-aldosterone system. Here, we show the first in vivo measurement of D1-like receptors in the renal cortex of Sprague-Dawley rat and Papio anubis baboon using [(11)C]NNC 112, a positron emission tomography radioligand for D1-like receptors. In addition, we show a D1-like binding potential response to angiotensin II blockade in rats using losartan. Demonstration of self-saturable binding in the rat as well as specific and saturable binding in Papio anubis validate the use of [(11)C]NNC 112 in the first in vivo measurement of renal dopamine D1-like receptors. Furthermore, [(11)C]NNC 112 is a radioligand tool already validated for use in probing human central nervous system (CNS) D1-like receptors. Our work demonstrates specific and saturable non-CNS binding in higher animals and the ability to quantify physiological response to drug treatment and provides a clear path to extend use of [(11)C]NNC 112 to study renal dopamine in humans.